The ability to control gene expression is essential for neurons of the central nervous system to respond appropriately to changes in the environment. These changes include normal experience as well as compensatory or regenerative changes following injury. In spinal cord pathways that relay and process information about pain, some neurons modify their cellular or functional characteristics in response to experience, painful stimuli or injury. The PI wishes to determine whether the control of gene expression via retinoic acid (vitamin A), a steroid-like hormone that influences the initial development of neurons in dorsal horn of the embryonic spinal cord, contributes to this capacity for change in the mature cord. Preliminary observations show that a distinct subpopulation of cells in lamina I, II and III of the dorsal horn activate gene expression via retinoic acid signaling throughout life. The P.I. proposes to establish the relationship between these retinoid-activated cells and neurons that process and relay pain information in the dorsal spinal cord. Furthermore, the P.I. will evaluate whether retinoic acid activation of gene expression can contribute to changes in transcription in dorsal horn neurons that are seen following injury. The control of gene expression by retinoic acid may be related to the modulation of expression of immediate early genes like c-fos and the subsequent increase in expression of opiod and other peptide neurotransmitters as well as their receptors in the dorsal horn. Accordingly, Dr. Lamantia will determine whether the cells that respond transcriptionally to retinoids have distinct connectional and biochemical properties as well as the capacity to modify gene expression in response to peripheral trauma or deafferentation. Thus, the experiments in this proposal will allow the PI to evaluate critically the hypothesis that a distinctive transcriptional control mechanism used during development of the spinal cord-retinoid mediated transcriptional activation- subsequently contributes to cellular and functional plasticity in specific populations of neurons in the mature spinal cord.